Products

2-Thiophenecarbonitrile

2-Thiophenecarbonitrile

2-Thiophenecarbonitrile

CAS No.: 1003-31-2

Category Products

Cat.NO.:A560039 Purity:98%

Product Details of [ 1003-31-2 ]

CAS No. :	1003-31-2
Formula :	C₅H₃NS
M.W :	109.15
SMILES Code :	C1=C(SC=C1)C#N
MDL No. :	MFCD00005416
InChI Key :	CUPOOAWTRIURFT-UHFFFAOYSA-N
Pubchem ID :	66087

Safety of [ 1003-31-2 ]

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H225-H302-H312-H314
Precautionary Statements:	P280-P303+P361+P353-P305+P351+P338-P310
Class:	3(8)
UN#:	2924
Packing Group:	Ⅲ

Computational Chemistry of [ 1003-31-2 ] Show Less

Physicochemical Properties

Num. heavy atoms	7
Num. arom. heavy atoms	5
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	1.0
Num. H-bond donors	0.0
Molar Refractivity	29.03
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	52.03 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.56
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.27
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.62
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	0.37
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.55
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.47

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.85
Solubility	1.56 mg/ml ; 0.0143 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.96
Solubility	1.19 mg/ml ; 0.0109 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-1.69
Solubility	2.24 mg/ml ; 0.0205 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.06 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12’782’590 molecules and tested on 40 external molecules (r² = 0.94)	2.07

Application In Synthesis of [ 1003-31-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 1003-31-2 ]

[ 1003-31-2 ] Synthesis Path-Downstream 1~8

1
[ 1003-31-2 ]
[ 21512-16-3 ]

Yield	Reaction Conditions	Operation in experiment
6.9 g (84%)	With n-butyllithium; diisopropylamine; citric acid; In tetrahydrofuran; N-methyl-acetamide; water; ethyl acetate;	EXAMPLE 65 STR100 A) Preparation of 2-cyano-5-formylthiophene To a flame-dried 3 neck 1 L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere. The flask was cooled to an internal temperature of -78° C. (dry ice/acetone). To this stirring solution was added n-butyllithium (1.6 M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min. To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min. The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe. This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL). Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each). Layers were separated and the aqueous phase was washed once with diethyl ether. The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50percent ethyl acetate/hexanes). Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84percent) of 2-cyano-5-formyl-thiophene.
6.9 g (84%)	With n-butyllithium; diisopropylamine; citric acid; In tetrahydrofuran; N-methyl-acetamide; water; ethyl acetate;	EXAMPLE 65 STR95 A) Preparation of 2-cyano-5-formylthiophene To a flame-dried 3 neck 1L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere. The flask was cooled to an internal temperature of -78° C. (dry ice/acetone). To this stirring solution was added n-butyllithium (1.6M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min. To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min. The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe. This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL). Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each). Layers were separated and the aqueous phase was washed once with diethyl ether. The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50percent ethyl acetate/hexanes). Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84percent) of 2-cyano-5-formyl-thiophene.
6.9 g (84%)	With n-butyllithium; diisopropylamine; citric acid; In tetrahydrofuran; N-methyl-acetamide; water; ethyl acetate;	A) Preparation of 2-cyano-5-formylthiophene To a flame-dried 3 neck 1L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere. The flask was cooled to an internal temperature of -78° C. (dry ice/acetone). To this stirring solution was added n-butyllithium (1.6M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min. To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min. The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe. This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL). Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each). Layers were separated and the aqueous phase was washed once with diethyl ether. The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50percent ethyl acetate/hexanes). Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84percent) of 2-cyano-5-formyl-thiophene.

6.9 g (84%)	With n-butyllithium; diisopropylamine; citric acid; In tetrahydrofuran; N-methyl-acetamide; water; ethyl acetate;	EXAMPLE 65 STR106 A) Preparation of 2-cyano-5-formylthiophene To a flame-dried 3 neck 1 L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere. The flask was cooled to an internal temperature of -78° C. (dry ice/acetone). To this stirring solution was added n-butyllithium (1.6M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min. To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min. The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe. This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL). Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each). Layers were separated and the aqueous phase was washed once with diethyl ether. The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50percent ethyl acetate/hexanes). Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84percent) of 2-cyano-5-formyl-thiophene.
50%Chromat.		A solution of diisopropylamine (35.3 ml, 0.251 moles) in tetrahydrofuran (500 ml) was cooled to -78 C. under a nitrogen blanket. To this was added 1.6M n-butyllithium in hexanes (157 ml, 0.251 moles) and allowed to stir for 5 min. Then slowly added thiopene-2-carbonitrile (21.33 ml, 0.229 moles) in tetrahydrofuran (115 ml) and allowed to stir. After 45 min. was added NN-dimethylformamide (88.66 ml, 1.145 moles) at -78 C. Citric acid (40 g) was added after 2 h. followed by water (240 ml) and stirred for 18 h. The reaction was concentrated in vacuo, transferred to a separatory funnel, diluted with brine, and extracted twice with ether. The combined ether layers were washed with brine, dried over magnesium sulfate, filtered, and the solvent removed in vacuo. Chromatography yielded 15.8 g (50percent) of 2-cyano-5-formylthiophene (EX-55A) as a brown solid: 1H NMR (300 MHZ, CDCl3) d 10.02 (s, 1H), 7.79 (m, 1H), 7.30 (m, 1H).

References: [1]Patent: US5914319,1999,A .
[2]Patent: US5707966,1998,A .
[3]Patent: US5710130,1998,A .
[4]Patent: US5726159,1998,A .
[5]Patent: US6664255,2003,B1 .Location in patent: Page column 117.

2
[ 1003-31-2 ]
[ 68-12-2 ]
[ 21512-16-3 ]

Yield	Reaction Conditions	Operation in experiment
76%		Method C5- Formylthiophene-2-carbonitrile (Intermediate compound)Under inert atmosphere BuLi (1 1 .7 ml, 29.3 mmol, 2.5 M) was added to a mixture of diisopropylamine (4.1 ml, 29.3 mmol) and THF (150 ml) at below – 70°C. When addition was finished, the mixture was allowed to reach room- temperature. The mixture was cooled back to -70°C again, where 2- thiophenecarbonitrile (3.0 g, 26.7 mmol), solved in THF (15 ml) was added drop- wise and stirred an additional hour. At -78°C. DMF (8.2 ml, 106.6 mmol) was added below -70°C. The mixture was stirred for 1 .5 h at -78°C. Citric acid (10 g) was added to the reaction-mixture. The reaction-mixture was poured out on water. The aqueous phase was extracted with diethylether. The product was dried and evaporated. The reaction mixture was purified by silica gel column chromatography using 10-50percent heptane/EtOAc as solvent. The product was isolated as a solid. Yield 2.8 g (76percent).
		5-formylthiophene-2-carbonitrile A tetrahydrofuran solution (250 mL) of lithium diisopropyl amide (1.09N hexane solution, 92.8 mL, manufactured by Kanto Chemical Co., Inc) was cooled down at -78° C., and a tetrahydrofuran solution (50 mL) of 2-cyanothiophene (8.55 mL, manufactured by Aldrich) was dropped thereto. After that, the resultant mixture was stirred for 45 minutes at the same temperature, N,N-dimethyl formamide (30 mL, manufactured by Kanto Chemical Co., Inc) was added to the mixture, and the resultant blend was stirred for 1 hour. After the stirring was ended, citric acid (20 g, manufactured by Wako Pure Chemical Industries, Ltd.) was added to the reaction solution and the resultant was poured into water. After tetrahydrofuran was distilled away, extraction was performed by using diethyl ether. An organic layer was washed with a saturated saline solution, and dried by using magnesium sulfate. After concentrating at a reduced pressure, chromatography (as an elution solution, 4:1 (v/v) of hexane/ethyl acetate was used) using Biotage 40M cartridge was performed, so that the titled compound (7.45 g) was obtained. 1H-NMR (CDCl3): 10.0 (1H, s), 7.77 (1H, d, J=3.3), 7.74 (1H, d, J-3.3)

References: [1]Patent: WO2011/73298,2011,A1 .Location in patent: Page/Page column 18.
[2]Patent: US2008/200535,2008,A1 .Location in patent: Page/Page column 169.

3
[ 1003-31-2 ]
[ 1455-20-5 ]
[ 1322575-28-9 ]

References: [1]Journal of the American Chemical Society,2011,vol. 133,p. 13577 – 13586.

4
[ 1003-31-2 ]
[ 1000623-95-9 ]

References: [1]Dyes and Pigments,2012,vol. 95,p. 126 – 133.
[2]RSC Advances,2014,vol. 4,p. 58027 – 58035.
[3]Electrochimica Acta,2014,vol. 144,p. 211 – 220.
[4]RSC Advances,2015,vol. 5,p. 19520 – 19527.
[5]Dyes and Pigments,2016,vol. 127,p. 37 – 44.
[6]Patent: CN103360397,2016,B .
[7]Journal of Fluorescence,2016,vol. 26,p. 1939 – 1949.
[8]Patent: US9590187,2017,B2 .
[9]Journal of Heterocyclic Chemistry,2017,vol. 54,p. 1983 – 1994.
[10]Patent: CN108794490,2018,A .

5
[ 1003-31-2 ]
[ 1000623-95-9 ]
[ 1269004-58-1 ]

References: [1]Journal of Materials Chemistry A,2013,vol. 1,p. 2795 – 2805.

6
[ 188290-36-0 ]
[ 1003-31-2 ]
[ 704-38-1 ]

References: [1]Advanced Synthesis and Catalysis,2014,vol. 356,p. 369 – 373.

7
[ 1003-31-2 ]
Details

Reviews

There are no reviews yet.

Be the first to review “2-Thiophenecarbonitrile”

Previous

1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrrolidin-2-one

Next

Benzofuran-5-carbaldehyde